Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia
clinical immunology/immunity therapeutics
Authors: Z. Leng et al.
Journal/ Pre-Print: Aging and disease
Key Words: COVID-19, ACE2 negative, mesenchymal stem cells, cell transplantation, immunomodulation,
1. The intravenous infusion of MSCs is a safe and effective approach even for severe and critical Covid-19 patients. MSCs are found to be ACE-2 negative having natural immunity to coronavirus.
2. All 7 patients were recovered due to MSCs immunomodulatory effect, MSCs reversed the elevated cytokine storms to normal level.
3. Significant downregulation of pro-inflammatory cytokines (CRP, TNF-a etc) and overactivated cytokine secreting immune cells were suppressed (CXCR3+, CD4+TCells etc). In contrast, up-regulation of anti-inflammatory DC, IL10 was observed.
The main rationale for this study was that MSCs having immunomodulatory characteristics could fight against cytokine storms. Cytokine storms is the cause of death in several COVID-19 patients.
Total 10 COVID-19 patients are considered for this pilot study. Seven COVID-19 patients were given intravenous infusion of MSCs. These seven experimental patients were categorized as, four severe, two with mild symptoms and one critically ill. Interestingly, after 14 days, all these seven patients were recovered. While, sever placebo control group depicts different outcome, one died, one developed ARDS, and one observed to be in stable condition.
IMPACT FOR SARS-COV2/COVID19 RESEARCH EFFORTS
A cell biological-therapeutic approach confronting the cytokine storm in Covid-19 patients.
Covid-19 Patient Case study (small scale).
STRENGTHS AND LIMITATIONS OF THE PAPER
Novelty: Authors introduced MSC for the first time as an ACE-2 negative and TMPRSS2 negative cell source. MSC secrete anti-inflammatory factors which can fight against cytokines storm.
Standing in the field: No, previously, just a single study on single patient has been reported by B. Liang et al. ChinaXiv, 202002.00084, 2020.
Viral model used: No, applied directly on COVID-19 patients.
Translatability: Yes, there is a potential in the idea, but to validate these preliminary findings, a larger cohort of patients are required.
Main limitations: First, the disease is so capricious and subjects’ numbers are so tiny. So, to make the efficacy trustworthy, the study needs to be powered up. Second, there is big question mark on safety, as we know MSCs suppress immunity, which can make the subject more vulnerable or could subside the immune response to coronavirus. So, we don’t know the safety records of these particular groups of patients. Thirdly, two patients in the control group with worst outcome (one died, one developed ARDS) were 10 year older than the oldest patient in the experimental group, which could raise age limitation issues.